Bupropioonravi depressiooni korral: mono- ja kombinatsioonteraapia

Bupropioon on ainus dopamiini ning noradrenaliini tagasihaarde inhibiitor, mis on näidustatud depressiivse häire ja aastaajast sõltuva meeleoluhäire raviks, olles kliiniliste uuringute põhjal niisama tõhus kui teised antidepressandid. Kakskümmend aastat kliinilist praktikat kinnitab bupropiooni ohutust ning efektiivsust, seega on ta kasutatav esimese valiku preparaadina. Üha enam tõendeid räägib ka bupropiooni kasutamise poolt juhtudel, kui depressiivne sümptomaatika serotoniini tagasihaarde inhibiitorite abil ei taandu või taandub vaid osaliselt. Mitmed uuringud kinnitavad bupropiooni eeliseid serotoninergiliste antidepressantide ees melanhoolsete sümptomite ravis. Ülevaates on keskendutud bupropioonravi eelistele depressiivsete patsientide ravis, et optimeerida selle kasutamist arstlikus praktikas. Eesti Arst 2010; 89(2):113−11

Bupropiooni augmentatsiooni toime estsitalopraamravi suhtes resistentsetel depressiivsetel patsientidel

Üha enam on andmeid, et bupropioon on üks efektiivsemaid valikuid augmentatsiooniks neil depressiivsetel patsientidel, kes serotoniini tagasihaarde inhibiitoritele reageerivad osaliselt või mitteküllaldaselt. Käesolevas uuringus jälgiti bupropiooni augmentatsiooni efektiivsust ja talutavust estsitalopraamravile mittereageerinud patsientidel. Seisundi kliinilist raskusastet ja paranemist hinnati kahenädalase intervalliga, kasutades selleks erinevaid skaalasid. Patsiendid hindasid sümptomeid ja võimalikke kõrvaltoimeid enesehinnangulistel skaaladel. Sarnaselt eelnevate uuringutega leiti, et bupropiooni augmentatsioon oli üldiselt hästi talutav ja aitas edukalt saada ravivastust enamikul serotoniini tagasihaarde inhibiitori monoteraapia suhtes resistentsetel patsientidel. Melanhoolset tüüpi depressioon oli seotud ebapiisava või osalise ravivastusega estsitalopraamile. Tulemused toetasid seisukohta, et bupropioon on esmavaliku antidepressant melanhoolse depressiooni ravis. Eesti Arst 2009; 88(2):82−9

Polymorphisms in the interleukin-10 gene cluster are possibly involved in the increased risk for major depressive disorder

<p>Abstract</p> <p>Background</p> <p>Innate immune inflammatory response is suggested to have a role in the pathogenesis of major depressive disorder (MDD). Interleukin (IL)-10 family cytokines IL-10, IL-19, IL-20, and IL-24 are all implicated in the inflammatory processes and polymorphisms in respective genes have been associated with various immunopathological conditions. This study was carried out to investigate whether single-nucleotide polymorphisms (SNPs) in these genes are also associated with MDD.</p> <p>Methods</p> <p>Case-control association study was performed with seven SNPs from the <it>IL10 </it>gene cluster. 153 patients with MDD and 277 healthy control individuals were recruited.</p> <p>Results</p> <p>None of the selected SNPs were individually associated with MDD. The linkage disequilibrium (LD) analysis indicated the existence of two recombination sites in the <it>IL10 </it>gene cluster, thus confirming the formerly established LD pattern of this genomic region. This also created two haplotype blocks, both consisting of three SNPs. Additionally, the haplotype analysis detected a significantly higher frequency of block 2 (<it>IL20 </it>and <it>IL24 </it>genes) haplotype TGC in the patients group compared to healthy control individuals (P = 0.0097).</p> <p>Conclusion</p> <p>Our study established increased risk for MDD related to the <it>IL20 </it>and <it>IL24 </it>haplotype and suggests that cytokines may contribute to the pathogenesis of MDD. Since none of the block 2 SNPs were individually associated with MDD, it is possible that other polymorphisms linked to them contribute to the disease susceptibility. Future studies are needed to confirm the results and to find the possible functional explanation.</p

Immunoloogilised muutused unipolaarse depressiooni korral ja antidepressiivse ravi käigus

Väitekirja elektroonilisest versioonist puuduvad väitekirja aluseks olevate artiklite täistekstidThe purposes of this study were to find associations between depression, depressive symptoms and soluble interleukine- 2 receptor (sIL-2R), tumour necrosis factor-α (TNF-α) and anti thyroid peroxidise auto-antibodies (anti-TPO). We investigated the acute and chronic effects of selective serotonin re-uptake inhibitor, escitalopram, alone and in combination with bupropion on serum levels of interleukin-8 (IL-8), sIL-2R and TNFα in patients with major depression. In addition, we explored whether serum cytokine concentrations and/or anti-TPO positivity can predict treatment response to antidepressants. The levels of TNF-α were lower in currently depressed subjects compared with euthymic subjects in the study cohort. MDD patients with previous antidepressive treatment had significantly lower levels of TNF-α than drug-naïve patients and HC. There were different patterns of changes in the levels of sIL-2R in responders and non-responders to escitalopram treatment. Treatment with escitalopram had no significant effect on the levels of IL-8 and TNF-α. Augmentation of escitalopram treatment with bupropion caused a significant increase in IL-8 serum concentrations during 6 weeks of augmentation therapy. There was no effect on the levels of sIL-2R and TNF-α. The lower baseline TNF-α level was found in the responder group in the escitalopram treatment phase. There was a trend for higher frequency of baseline anti-TPO positive cases in female non-responders to escitalopram monotherapy as compared with responders. There were no significant differences in the levels of thyroid hormones (particularly, total T3, free T3, freeT4, and TSH) between female responders and non-responders.Käesoleva uurimuse eesmärgiks oli seoste leidmine depressiooni, depressiivsete sümptomite ja lahustuva interleukiin-2 retseptori (sIL-2R), tuumor-nekroosfaktor alfa (TNF-α) ning türoid-peroksidaasi autoantikehade vahel (anti-TPO). Me uurisime ka selektiivse serotoniini tagasihaarde inhibiitori, estsitalopraami lühi- ja pikaajalist mõju seerumi interleukiin-8-le (IL-8), sIL-2R-le ja TNFα depressiivsetel patsientidel monoteraapias ja kombinatsioonis bupropiooniga. Lisaks selgitasime, kas seerumi tsütokiinide kontsentratsioon ja/või anti-TPO positiivsus võib ennustada ravivastust antidepressandile. Depressiivsetel patsientidel oli madalam TNF-α tase võrreldes eutüümsete isikutega. Depressioonipatsientidel, kes olid eelnevalt elu jooksul saanud antidepressantravi, oli oluliselt madalam TNF-α tase kui tervetel kontrollisikutel ja eelneva ravita patsientidel. sIL-2R muutused olid erinevad estsitalopraamravile reageerinud ja mittereageerinud patsientidel. Ravi estsitalopraamiga ei mõjutanud oluliselt IL-8 ja TNF-α taset. Estsitalopraami kombineerimine bupropiooniga 6 nädala vältel põhjustas IL-8 taseme tõusu seerumis, sIL-2R ja TNF-α. kontsentratsioonid oluliselt ei muutunud. Ravieelne TNF-α tase oli estsitalopraamravile reageerinud patsientidel madalam kui raviresistentsetel isikutel. Esines tendents, et raviresistentsete naispatsientide hulgas oli enam anti-TPO positiivseid isikuid kui ravile reageerinute hulgas. Naispatsientide ja tervete naiste vahel ei ilmnenud erinevust türoidhormoonide osas (täpsemalt kogu T3, vaba T3, vaba T4 ja TSH)

Soluble interleukin-2 receptor and tumor necrosis factor levels in depressed patients in Estonia

Several studies have reported immune system alterations in depressed patients. Furthermore, correlations between some interleukins and specific depressive symptoms have been found, but results are ambiguous. It might be caused by heterogeneous patient population and concomitant administration of antidepressants. The aim of our study was to look at differences in the levels of soluble interleukin-2 receptor (sIL-2R) and tumor necrosis factor-α (TNFα) between currently depressed patients with first or recurrent episode of depression, patients in full remission and healthy controls. Secondly, we looked for correlations between sIL-2R and TNFα and different depressive symptoms. A total of 75 medication-free currently depressed patients (76% of females), 17 patients in the full remission phase of major depression (58.8% of females), and 55 healthy controls (58.2% of females) participated in this study. The results showed that the level of sIL-2R was significantly lower in depressed patients in remission phase compared to the healthy controls and subjects with recurrent depression. Drug-naï ve patients with major depressive disorder with recurrent episode had higher levels of sIL-2R than previously treated or patients with the first episode. TNFα levels were higher in drug-naï ve patients with major depressive disorder with recurrent episode compared with previously treated patients. Further analysis of patients revealed that sIL-2R was positively correlated with decreased activity and agitation. TNFα was associated with decreased activity and suicidality

Whole-exome sequencing identifies a polymorphism in the BMP5 gene associated with SSRI treatment response in major depression

Although antidepressants are widely used in the pharmacotherapy of major depressive disorder (MDD), their efficacy is still insufficient as approximately one-third of the patients do not fully recover even after several treatment trials. Inter-individual genetic differences are thought to contribute to the variability in antidepressant response; however, current findings from pharmacogenetic studies are uncertain or not clearly replicated. Here we report the first application of full exome sequencing for the analysis of pharmacogenomics on antidepressant treatment. After 12 weeks of treatment with the selective serotonin re-uptake inhibitor escitalopram, we selected five clear responders and five clear non-responders for exome sequencing. By comparing the allele counts of previously known single nucleotide polymorphisms and novel polymorphisms we selected 38 markers for further genotyping in two independent patient samples treated with escitalopram (n=116 and n=394). The A allele, carried by approximately 30% of the patients with MDD, of rs41271330 in the bone morphogenetic protein (BMP5) gene showed strong association with worse treatment response in both sample sets (p=0.001), indicating that this is an promising pharmacogenetic marker for prediction of antidepressant therapeutic outcome